Kill-painting of hypoxic tumours in charged particle therapy
Kill-painting of hypoxic tumours in charged particle therapy
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DOI：
10.1038/srep17016
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发表时间：
2015-11-24
影响因子：
4.6
通讯作者：
Scifoni, Emanuele
中科院分区：
文献类型：
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作者：
Tinganelli, Walter;Durante, Marco;Scifoni, Emanuele
实体肿瘤通常表现为严重缺氧，对化疗和放疗都有耐药性。对x射线来说，随着氧浓度的增加而增加的辐射灵敏度已经得到了很好的描述。研究还表明，在缺氧情况下，使用高let辐射而不是传统的x射线可以降低辐射抗性。然而，氧增强比（OER）对中等氧浓度区域（通常在肿瘤中发现的区域）辐射质量的依赖性从未被测量过，生物物理模型是基于推断的。在这里，我们提供了一个完整的哺乳动物细胞存活数据集，这些细胞暴露于氧气浓度从常氧（21%）到缺氧（0%）的不同离子中。这些数据被用于生成OER对氧浓度和粒子能量依赖的模型。该模型在离子束治疗计划系统中实现，以规定具有异质放射敏感性的均匀细胞杀伤。适应性治疗计划已经在两种不同的加速器设施中得到验证，使用生物幻影，细胞可以在三种不同的氧浓度下同时照射。因此，我们实现了一个适应缺氧的治疗方案，该方案将用于缺氧肿瘤的体素绘制，通过功能成像可视化。
Solid tumours often present regions with severe oxygen deprivation (hypoxia), which are resistant to both chemotherapy and radiotherapy. Increased radiosensitivity as a function of the oxygen concentration is well described for X-rays. It has also been demonstrated that radioresistance in anoxia is reduced using high-LET radiation rather than conventional X-rays. However, the dependence of the oxygen enhancement ratio (OER) on radiation quality in the regions of intermediate oxygen concentrations, those normally found in tumours, had never been measured and biophysical models were based on extrapolations. Here we present a complete survival dataset of mammalian cells exposed to different ions in oxygen concentration ranging from normoxia (21%) to anoxia (0%). The data were used to generate a model of the dependence of the OER on oxygen concentration and particle energy. The model was implemented in the ion beam treatment planning system to prescribe uniform cell killing across volumes with heterogeneous radiosensitivity. The adaptive treatment plans have been validated in two different accelerator facilities, using a biological phantom where cells can be irradiated simultaneously at three different oxygen concentrations. We thus realized a hypoxia-adapted treatment plan, which will be used for painting by voxel of hypoxic tumours visualized by functional imaging.